Institute of Toxicology, College of Preventive Medicine, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, PR China.
Institute of Toxicology, College of Preventive Medicine, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, PR China.
Toxicol Lett. 2018 Oct 15;296:163-172. doi: 10.1016/j.toxlet.2018.06.1067. Epub 2018 Jun 15.
Roundup® is extensively used for weed control worldwide. Residues of this compound may lead to side effects of the male reproductive system. However, the toxic effects and mechanisms of Roundup® of male germ cells remain unclear. We aimed to investigate the apoptosis-inducing effects of Roundup® on mouse male germ cells and explore the role of a novel tumor suppressor XAF1 (X-linked inhibitor of apoptosis-associated factor 1) involved in this process. We demonstrated that Roundup® can impair spermatogenesis, decrease sperm motility and concentration, and increase the sperm deformity rate in mice. In addition, excessive apoptosis of germ cells accompanied by the overexpression of XAF1 occurred after Roundup® exposure both in vitro and in vivo. Furthermore, the low expression of XIAP (X-linked inhibitor of apoptosis) induced by Roundup® was inversely correlated with XAF1. Moreover, the knockdown of XAF1 attenuated germ cell apoptosis, improved XIAP expression and inhibited the activation of its downstream target proteins, caspase-3 and PARP, after Roundup® exposure. Taken together, our data indicated that XAF1 plays an important role in Roundup®-induced male germ cell apoptosis. The present study suggested that Roundup® exposure has potential negative implications on male reproductive health in mammals.
农达®在世界范围内广泛用于杂草控制。该化合物的残留可能导致男性生殖系统的副作用。然而，农达®对雄性生殖细胞的毒性作用和机制尚不清楚。我们旨在研究农达®对雄性小鼠生殖细胞的诱导凋亡作用，并探讨在此过程中涉及的新型肿瘤抑制因子 XAF1（X 连锁凋亡抑制因子相关因子 1）的作用。我们证明，农达®可损害精子发生，降低精子活力和浓度，并增加小鼠精子畸形率。此外，在体外和体内暴露于农达®后，生殖细胞过度凋亡伴随着 XAF1 的过度表达。此外，农达®诱导的 XIAP（凋亡抑制蛋白 X 连锁抑制因子）的低表达与 XAF1 呈负相关。此外，XAF1 的敲低可减弱农达®暴露后的生殖细胞凋亡，提高 XIAP 表达并抑制其下游靶蛋白 caspase-3 和 PARP 的激活。综上所述，我们的数据表明 XAF1 在农达®诱导的雄性生殖细胞凋亡中发挥重要作用。本研究表明，农达®暴露对哺乳动物的男性生殖健康具有潜在的负面影响。
